Relative and absolute amounts of body fat are critical for the onset of puberty and subsequent development and maintenance of menstrual cyclicity, ovulation and ultimately fertility. Obese prepubertal girls exhibit accelerated maturation and show clinical and biochemical evidence of an activated hyopothalamic-gonadal axis (or puberty onset) at an earlier age. The incidence of obesity in children is rising and becoming a significant public health concern and the effect of weight reduction programs on the pubertal maturation of obese children need to be determined. In contrast, lean athletic post-pubertal girls and young women have an increased incidence of menstrual cycle disruption and show clinical and biochemical evidence of involution of their hypothalamic-gonadal axis. As a growing number of school-age girls and young women enroll in competitive athletic programs, the deleterious effects of exercise on the female reproductive axis are becoming more prevalent. High intensity and sustained exercise regimens may induce amenorrhea in otherwise healthy young women. The observation in obese and exercising girls coupled with emerging data in animal models suggest that adipose tissue has a permissive role in the matuation of the hypothalamic-gonadal axis. Leptin, the recently characterized adipocyte-derive hormone has been proposed to establish the metabolic link between adipose tissue and the central-nervous system. Studies described in this proposal will test the hypothesis that the adipocyte- derived hormone, leptin, regulates the state of maturation of the hypothalamic- pituitary-gonadal axis. The hypothesis will be tested utilizing two models: the obese girl with precocious puberty and the lean post-pubertal athlete with secondary amenorrhea and reproductive immaturity. To determine whether increased leptin concentrations correlate with accelerated activation of the reproductive axis, we will relate changes in circulating gonadotropins and leptin concentraion in prepubertal obese girls with evidence of early pubertal development and lean, age and bone-age matched, controls. This initial study will be followed by an intervention experiment of four months' duration with dietary restriction and increased physical activity in the early pubertal obese girls. Comparative assesment of leptin and gonadotropins concentrations both before and after weight and adiposity reduction should provide a handle on whether de-activation of the reproductive axis is related to a low leptin state, we will relate circulating gonadotropin and leptin concentrations in three groups of post-pubertal very young women:amenorrheic athletes (AA) cyclic athletes (CA), and cyclic sedentary (CS). In addition, intervention experiments will be performed in cyclic sedentary controls by imposing a four months' period of increased physical activity to determine if expected changes inmenstrual cyclicity will relate to decreased adiposity and leptin concentrations.